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Biomedical subjects

J Fisher

Publications and source records attributed to J Fisher.

At least 73 records · Page 4Linked to original sources

Harming and benefiting the dead.

The traditional view of grief resolution requires the bereaved person to disengage from the deceased. This is often expressed as a necessary "letting go" of the past for the survivor to be free to continue her or his life and form new relationships. Contemporary grief theory, in contrast, recognizes that healthy grieving involves maintaining bonds with the deceased. The relationship between the bereaved person and the person who has died, although transformed, is ongoing. This article takes as its focus one aspect of the continuing relationship between the living and the dead. It begins with the noncontroversial claim that some actions that involve the dead are wrong from an ethical perspective. What is controversial is the explanation of the wrongness of these actions. It is argued that the dead can be harmed by having their interests thwarted and, conversely, they can be benefited by having their interests promoted. Posthumous harm and benefit are possible because people who are now dead possessed interests prior to death that continue to exert a claim after death.

Conflict of Interest↗

Maternal milk consumption predicts the tradeoff between milk and soft drinks in young girls' diets.

Milk intake constitutes an important source of dietary calcium for young girls but declines throughout childhood. Recent work shows that the intake of soft drinks may contribute to this decline. Influences on the apparent tradeoff between soft drinks and milk in young girls' diets are not well described. The objective of this research was to test a model depicting maternal beverage choices as predictors of their daughters' milk and soft drink intake. A structural equation model describing maternal influences on daughters' milk, soft drink and calcium intakes was tested using data from 180 non-Hispanic, white families with 5-y-old daughters. Mothers' calcium, milk and soft drink intakes were evaluated as predictors of their daughters' intakes. Mothers' and daughters' soft drink intakes were also examined as predictors of their own milk and calcium intakes. The model provided a good fit to the data, revealing mother-daughter similarities in beverage intake. Mothers who drank milk more frequently had daughters who drank milk more frequently and drank fewer soft drinks. For both mothers and daughters, soft drink consumption was negatively related to both milk and calcium intake. This research provides evidence that mothers' beverage choices influence the tradeoff between milk and soft drinks in their daughters' diets. In particular, mothers' milk and soft drink intakes may affect their daughters' calcium adequacy in early childhood by influencing the frequency with which their daughters consume those beverages.

Adult↗

Influence of simulator kinematics on the wear of metal-on-metal hip prostheses.

There is now considerable interest in metal-on-metal bearings for hip prostheses. Extremely low wear rates (0.1 mm3/10(6) cycles) have been reported in some simulator studies, while in vivo studies, although still very low, have shown wear rates of the order of 1 mm3/10(6) cycles. The aim of this study was to compare wear rates of metal-on-metal bearings in two hip simulators with different kinematic inputs. In the simulator with three independent input motions which produced an open elliptical wear path with a low level of eccentricity, the wear rates were very low as recorded previously in other simulators. In the simulator with two input motions which produced an open elliptical wear path with greater eccentricity the wear rate was at least ten times higher and closer to clinical values. The motion and kinematic conditions in the contact are critical determinants of wear in metal-on-metal bearings.

Biomechanical Phenomena↗

A novel method for the prediction of functional biological activity of polyethylene wear debris.

The comparative performance of artificial hip joints has been extensively investigated in vitro through measurements of wear volumes. In vivo a major cause of long-term failure is wear-debris-induced osteolysis. These adverse biological reactions are not simply dependent on wear volume, but are also controlled by the size and volumetric concentration of the debris. A novel model is presented which predicts functional biological activity; this is determined by integrating the product of the biological activity function and the volumetric concentration function with the wear volume over the whole particle size range. This model combines conventional wear volume measurements with particle analysis and the output from in vitro cell culture studies to provide a new indicator of osteolytic potential. The application of the model is demonstrated through comparison of the functional biological activity of wear debris from polyethylene acetabular cups articulating under three different conditions in a hip joint simulator.

Biocompatible Materials↗

The influence of phospholipid concentration in protein-containing lubricants on the wear of ultra-high molecular weight polyethylene in artificial hip joints.

There is considerable interest in the wear of polyethylene and the resulting wear-debris-induced osteolysis in artificial hip joints. Proteins play an important role as boundary lubricants in vivo in the pseudosynovial fluid, and these are reproduced in in vitro tests through the use of bovine serum. Little is known, however, about the effect of phospholipid concentrations within proteinaceous solutions on the wear of ultra-high molecular weight polyethylene (UHMWPE). The effects of protein-containing lubricants with 0.05, 0.5 and 5 per cent (w/v) phosphatidyl choline concentrations on the wear of ultra-high molecular weight polyethylene (UHMWPE) were compared with 25 per cent (v/v) bovine serum which had 0.01 per cent (w/v) lipid; the effects were compared in a hip joint simulator with smooth (n = 4) and scratched (n = 3) femoral heads. The control bovine serum lubricant produced UHWMPE wear of 55 and 115 mm3/10(6) cycles on the smooth and rough heads respectively. The increased phospholipid concentration significantly reduced the wear rate. At the higher concentration (5% w/v phosphatidyl choline) the average wear was reduced to less than 2 mm3/10(6) cycles. Even with the relatively low concentrations of 0.05% w/v phosphatidyl choline the wear was reduced by at least threefold compared with the bovine serum tests for both the smooth and rough femoral heads. There may be considerable differences in the phospholipid concentrations in patients' synovial fluid and this is highly likely to produce considerable variation in wear rates. In vitro, differences in the phospholipid concentration of lubricants may also cause variation in wear rates between different simulator tests.

Hip Prosthesis↗

Quantification of third body damage to the tibial counterface in mobile bearing knees.

Fourteen pairs of explanted low contact stress (LCS) tibial interface components: six rotating platform (RP), six meniscal (MN) and two anterior-posterior (AP) glide designs, have been analysed with particular attention paid to the condition of the tibial counterfaces. The average surface roughness, Ra, for the tibial trays ranged from 0.01 to 0.087 micron, significantly greater than the unworn control measurement of 0.008 micron. The scratch geometry analysis showed that the scratch peaks were found to be consistently of a lower aspect ratio than the scratch valleys and under 1 micron in height (average asperity height Rp = 0.52 micron, aspect ratio delta p = 0.01, average asperity depth Rv = 1.10 microns, delta v = 0.05). The largest scratches were 3-4 microns in both Rp and Rv. In vitro tests have shown that ultra-high molecular weight polyethylene (UHMWPE) wear increases in the presence of counterface scratches perpendicular to the direction of motion. In these explants, the unidirectional motion produced scratches parallel to the direction of sliding which is predicted to produce a smaller increase in UHMWPE wear. Other designs in mobile bearing knees have less constrained motion at the tibial counterface and this has been shown to accelerate wear; it may also lead to a further increase in wear in the presence of third body scratches. It may be possible in future knee designs to reduce this type of wear damage by introducing alternative materials or coatings which are more resistant to scratching and surface roughening.

Aged↗

A novel three-dimensional tissue equivalent model to study the combined effects of cyclic mechanical strain and wear particles on the osteolytic potential of primary human macrophages in vitro.

The effects of cyclic mechanical strain and challenge with physiologically relevant doses of submicrometre-size polyethylene (PE) particles on the osteolytic potential of primary human mononuclear phagocytes were investigated. Cells were seeded into a three-dimensional tissue matrix and co-cultured with particles (mean size 0.21 microm) at particle volume to cell number ratios of 7.5, 15, 30 and 100 microm3/cell. Matrices were then either cultured statically or subjected to 20 per cent cyclic compressional strain in the 'ComCell' for 16 h prior to the assessment of cell viability and quantification of the pro-inflammatory cytokine tumour necrosis factor alpha (TNFalpha). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazdium bromide) assay was shown to be too insensitive to detect changes in cell viability. However, when quantified by the adenosine triphosphate (ATP) assay, cell viability was demonstrated to be reduced following exposure to cyclic strain. Macrophages cultured in the static three-dimensional tissue equivalent model produced very high levels of TNFalpha in response to submicrometre PE particles at a ratio of 100 microm3/cell. Cyclic strain in the absence of particles gave only a small increase in TNFa production. However, the combined effects of strain and particle stimulation at a ratio of 30 microm3/cell resulted in the secretion of significantly more TNFalpha than was produced by macrophages subjected to strain alone, or the cells-only control. This synergy between cyclic strain and PE particle stimulation was only evident when the volume of particles was reduced below the volume that maximally stimulated cells. These results suggest that while cyclic strain may not be the primary factor responsible for macrophage activation and periprosthetic osteolysis, at low particle load, it may contribute significantly to the osteolytic potential of macrophages in vitro or in vivo.

Coculture Techniques↗

Importance of pin geometry on pin-on-plate wear testing of hard-on-hard bearing materials for artificial hip joints.

The contact mechanics between the pin and the plate used in simple wear screening tests were investigated in this study. Both soft-on-hard, such as ultra-high molecular weight polyethylene (UHMWPE)-on-metal or UHMWPE-on-ceramic, and hard-on-hard, such as metal-on-metal, bearing couples were considered. The effect of the pin geometry and the misalignment between the pin and the plate were investigated on the predicted contact pressure distribution at the bearing surfaces using the finite element method. It was demonstrated that in the case of soft-on-hard bearing couples, neither the geometrical discontinuity of the pin surface nor the misalignment could cause a significant increase in the contact stress. However, for hard-on-hard combinations, even with a very small misalignment of 0.5 degrees between the pin and the plate, the geometrical discontinuity could lead to a more than tenfold increase in the predicted contact stress. This elevated contact stress may lead to a large scatter in the wear data and, even more importantly, structural damage of the bearing surfaces.

Biomechanical Phenomena↗

A retrieval study of capital hip prostheses with titanium alloy femoral stems.

We have examined 26 retrieved, failed titanium-alloy femoral stems. The clinical details, radiological appearances and the histology of the surrounding soft tissues in each patient were also investigated. The stems were predominantly of the flanged design and had a characteristic pattern of wear. A review of the radiographs showed a series of changes, progressive with time. The first was lateral debonding with subsidence of the stem. This was followed by calcar resorption and fragmentation or fracture of the cement. Finally, osteolysis was seen, starting with a radiolucency at the cement-bone interface and progressing to endosteal cavitation. Three histological appearances were noted: granulomatous, necrobiotic and necrotic. We suggest that an unknown factor, possibly related to the design of the stem, caused it to move early. After this, micromovement at the cement-stem interface led to the generation of particulate debris and fracture of the cement. A soft-tissue reaction to the debris resulted in osteolysis and failure of fixation of the prostheses.

Aged↗

The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle.

In many patients with human immunodeficiency virus (HIV) treated with HIV protease inhibitors, a complication develops that resembles abdominal obesity syndrome, with insulin resistance and glucose intolerance that, in some cases, progresses to diabetes. In this study, we tested the hypothesis that indinavir, an HIV-protease inhibitor, directly induces insulin resistance of glucose transport in skeletal muscle. Rat epitrochlearis muscles were incubated with a maximally effective insulin concentration (12 nmol/l) and 0, 1, 5, 20, or 40 micromol/l indinavir for 4 h. In control muscles, insulin increased 3-O-[(3)H]methyl-D-glucose (3MG) transport from 0.15 +/- 0.03 to 1.10 +/- 0.05 micromol. ml(-)(1). 10 min(-)(1). Incubation of muscles with 5 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 40%, whereas 20 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 58%. Indinavir induced a similar reduction in maximally insulin-stimulated 3MG transport in the soleus muscle. The increase in glucose transport activity induced by stimulating epitrochlearis muscles to contract was also markedly reduced by indinavir. The insulin-stimulated increase in cell-surface GLUT4, assessed using the 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-[2-(3)H] (D-mannose-4-yloxy)-2-propylamine exofacial photolabeling technique, was reduced by approximately 70% in the presence of 20 micromol/l indinavir. Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B were not decreased by indinavir. These results provide evidence that indinavir inhibits the translocation or intrinsic activity of GLUT4 rather than insulin signaling.

Animals↗

A new design for polyurethane heart valves.

BACKGROUND AND AIM OF THE STUDY: The synthetic flexible tri-leaflet heart valve offers considerable potential for improvement in both hydrodynamic and biomechanical performance of replacement heart valves. To date, success with the synthetic leaflet heart valve has been limited, partly due to limitations in the biostability of the polyurethanes used. With the synthesis of new biostable polyurethanes, the integration of advancing technology, and better knowledge of the functional and biomechanical design requirements necessary to increase the long-term durability of the polyurethane heart valve, novel clinical solutions are now in sight. METHODS: This study describes the design characteristics, hydrodynamic and biomechanical performance of a new design of polyurethane heart valve. The function and durability characteristics of this novel design of heart valve, manufactured using a proven durable non-biostable polyurethane, was compared with that of a single AorTech porcine bioprosthetic heart valve and a single tilting disc mechanical heart valve, the Björk-Shiley Monostrut valve (BSM), of similar size. RESULTS: For equivalent sizes of valve, the new polyurethane heart valve design had significantly lower pressure gradients compared with the porcine valve at all flow rates and to the BSM valve at the higher flow rates. The effective orifice area of the polyurethane valve was greater than the other two valves studied; regurgitation and total energy loss were less. The new polyurethane valve design reached over 360 million cycles in an accelerated durability tester, without failure. CONCLUSION: This new design of polyurethane heart valve showed improved hydrodynamic function in comparison with either the porcine bioprosthetic or the BSM mechanical heart valve. The pulsatile flow results showed a lower total energy loss associated with this valve, indicating improved potential patient benefit. The durability of this new design of polyurethane heart valve was demonstrated when manufactured using a medical-grade polyurethane.

Biomechanical Phenomena↗

Hydrodynamic function of a biostable polyurethane flexible heart valve after six months in sheep.

Survival to six months for sheep with a non-biostable polyurethane mitral heart valve prosthesis has been reported previously, however, with surface degradation and accumulation of calcified fibrin/thrombus that impaired leaflet motion and compromised hydrodynamic function. Newly available biostable polyurethanes may overcome this problem. Six adult sheep with biostable polyurethane trileaflet heart valve prostheses of documented hydrodynamic performance, implanted in the mitral position, were allowed to survive for 6 months. Explanted valves were photographed, resubmitted to hydrodynamic function testing, and studied by light and electron microscopy. Explanted valves were structurally intact and differed little in appearance from their preimplant state. Hydrodynamic testing showed no deterioration in pressure gradient or energy losses compared with pre-implant values. Biostable polyurethanes demonstrated improved blood compatibility leaving leaflets flexible and valve function unimpaired. Biostable polyurethanes may thus improve prospects for prolonged function of synthetic heart valve prostheses.

Animals↗

Comparative wear and wear debris under three different counterface conditions of crosslinked and non-crosslinked ultra high molecular weight polyethylene.

The wear debris generated from ultra high molecular weight polyethylene (UHMWPE) have been recognised as one of the major causes of failure in total hip replacements (THR). It is essential to reduce the wear debris generated from UHMWPE acetabular cups in order to minimise this problem. Debris in the submicron size range is believed to have greater osteolytic potential. It is now known that crosslinked UHMWPE acetabular cups have reduced volumetric wear rates but little is known about the influence of crosslinking on the size and morphology of the wear debris. In this study, the wear of grade GUR 1020 crosslinked (vacuum gamma irradiated), GUR 1120 crosslinked (acetylene enhanced irradiated) and non cross linked (ethylene oxide sterilised) GUR 1020 UHMWPE was compared in multidirectional pin-on-plate wear tests under three different counterface conditions (smooth, isotropically rough and scratched counterfaces). Multidirectional motion was chosen because this motion was closer to the relative motion in the natural hip. From this study, better wear resistance of crosslinked UHMWPE compared with non-crosslinked UHMWPE was demonstrated for the smooth counterface conditions. However, in the rough and scratched counterface conditions, the vacuum gamma irradiated crosslinked material produced significantly higher wear rates than the non-crosslinked material. The analysis of the wear debris showed that the majority of the volume of the acetylene enhanced crosslinked UHMWPE wear debris was in the most biologically active size range (0.1 to 0.5 microm). In contrast, the non-crosslinked material and the vacuum gamma irradiated crosslinked material had a greater proportion of the volume of the debris in the larger size ranges which are less biologically active. This has important implications for its osteolytic potential.

Acetylene↗

A depth profile of oxidation and gel fraction in gamma-irradiated silane crosslinked and ultra high molecular weight polyethylenes.

The depth profile of oxidation index and gel fraction has been measured for two silane crosslinked poly(ethylene) (SXLPE) acetabular cups (one gamma irradiated in air, and one non-irradiated, both with a shelf-life of 13 years) and for two UHMWPE components (one gamma irradiated in air and one non-irradiated, with shelf-lives of 13 and 7 years, respectively). Only the irradiated UHMWPE exhibited any variation in these properties with depth. The oxidation profile (maximum 1 mm below surface) has been explained to result from reduced levels of diffused oxygen with depth, giving rise to a balance of alkyl and peroxyl radicals (and hence maximum carbonyl production) just below the surface. The gel fraction profile (maximum 4 mm below surface) is also attributed to the lower levels of diffused oxygen with depth, causing crosslinking to dominate in the bulk and chain scission to dominate at the surface. The resistance to oxidative degradation in the non-irradiated SXLPE was attributed to the use of antioxidants in the polymer processing.

Cross-Linking Reagents↗

The influence of ventricular input impedance on the hydrodynamic performance of bioprosthetic aortic roots in vitro.

BACKGROUND AND AIM OF THE STUDY: Hydrodynamic function testing using pulsatile flow simulators provides a valuable means of comparative assessment of heart valves in vitro. The majority of pulsatile flow simulators consist of modular rigid chambers and a positive displacement pump with an infinite input impedance, in which the inertia of the test fluid results in pressure oscillations when the valves under test are opening and closing. For mechanical and stented bioprosthetic valves these pressure oscillations decay quickly. However, due to the highly compliant nature of tissue roots, the resulting pressure and flow oscillations are extreme and extend throughout systole. With increasing interest in the use of free-sewn roots and valves it is most desirable to improve this hydrodynamic model. The aim of this study was to investigate the influence in changes in ventricular input impedance on the hydrodynamic characteristics of free-sewn aortic roots and stented valves. METHODS: The Leeds pulsatile flow simulator was modified to incorporate additional compliance chambers in the form of a viscoelastic impedance adaptor (VIA) at the pump/ventricular interface. Six 23 mm bioprosthetic aortic roots fixed with 0.5% buffered glutaraldehyde at zero pressure, and a size 23 mm stented porcine aortic bioprosthesis were tested in this modified simulator, at the conditions of maximum and minimum input compliance. RESULTS: The pressure and flow waveforms for the fixed aortic roots showed considerable differences at the conditions of maximum and minimum input compliance. Indeed, the extreme pressure oscillations observed at minimum compliance (infinite input impedance) were not present at maximum compliance, and the forward flow waveform was much smoother. In contrast, for the stented valve, the differences in the pressure and flow waveforms between maximum and minimum input compliance were minimal, but this was expected due to the lack of compliance in the stented valve itself. In addition, the flow and pressure waveforms at maximum compliance in the VIA were comparable for the fixed aortic roots and the stented bioprosthesis, thus allowing direct comparison of the characteristics of these two different devices. Using test conditions of maximum input compliance, effective orifice area for the roots was 1.69 cm2 compared with 1.47 cm2 for the stented valve. CONCLUSION: An appropriate physiological model for the hydrodynamic testing of compliant tissue roots has been established.

Aortic Valve↗

Simulation of tibial counterface wear in mobile bearing knees with uncoated and ADLC coated surfaces.

A multidirectional pin-on-plate reciprocating machine was used to compare the wear performance of UHMWPE sliding against cast cobalt chrome (CoCr) plates that were either untreated or coated with Amorphous Diamond Like Carbon (ADLC). The test conditions were based on a 1/5 scale model representative of in vivo motion at the tibial counterfaces of unconstrained mobile bearing knees. The average +/- STERR wear rates were 13.78+/-1.06 mm3/Mcycles for the ADLC counterfaces and 0.504+/-0.12 mm3/Mcycles for the control CoCr counterfaces. All of the pins run on the ADLC counterfaces exhibited the same patterns of blistering along the central axis, and severe abrasion elsewhere to the extent that all of the original machining marks were removed after just one week of testing. The average value of friction coefficient was 0.24 for the ADLC counterfaces and 0.073 for the control CoCr counterfaces. The factor of 3.5 increase was statistically significant at p < 0.05. In the tribological evaluation of ADLC coatings for tibial trays in mobile bearing knees, this study shows that this specific Physical Vapour Deposition (PVD) ADLC showed significantly poorer frictional and wear performance than uncoated surfaces which was sufficient to negate any potential benefits of improved resistance to third body damage.

Biocompatible Materials↗

Quantitative analysis of wear and wear debris from metal-on-metal hip prostheses tested in a physiological hip joint simulator.

Osteolysis and loosening of artificial joints caused by UHMWPE wear debris has prompted renewed interest in metal-on-metal (MOM) hip prostheses. This study investigated the wear and wear debris morphology generated by MOM prostheses in a physiological anatomical hip simulator for different carbon content cobalt chrome alloys. The low carbon pairings demonstrated significantly higher "bedding in" and steady state wear rates than the mixed and high carbon pairings. The in vitro wear rates reported here were up to one or two orders of magnitude lower than the clinical wear rates for first-generation MOM hip prostheses. Two methods for characterising the metal wear debris were developed, involving digestion, scanning electron microscopy and transmission electron microscopy. The metal wear particles characterised by the two methods were similar in size, 25-36 nm, and comparable to particles isolated from periprosthetic tissues from first and second-generation MOM hip prostheses. Due to the small size of the metal particles, the number of particles generated per year for MOM prostheses in vitro was estimated to be up to 100 times higher than the number of polyethylene particles generated per year in vivo. The volumetric wear rates were affected by the carbon content of the cobalt chrome alloy and the material combinations used. However, particle size and morphology was not affected by method of particle characterisation, the carbon content of the alloy or material combination.

Biomechanical Phenomena↗

Comparative analysis of two different types of alumina-alumina hip prosthesis retrieved for aseptic loosening.

We compared and quantified the modes of failure and patterns of wear of 11 Mittelmeier and 11 Ceraver-Ostal retrieved alumina-alumina hip prostheses with reference to the corresponding clinical and radiological histories. Macroscopic wear was assessed using a three-dimensional co-ordinate measuring machine. Talysurf contacting profilometry was used to measure surface roughness on a microscopic scale and SEM to determine mechanisms of wear at the submicron level. The components were classified into one of three categories of wear: low (no visible/measurable wear), stripe (elliptical wear stripe on the heads and larger worn areas on the cups) and severe (macroscopic wear, large volumes of material lost). Overall, the volumetric wear of the alumina-alumina prostheses was substantially less than the widely used metal and ceramic-on-polyethylene combinations. By identifying and eliminating the factors which accelerate wear, it is expected that the lifetime of these devices can be further increased.

Adolescent↗